1. Chapter 20 Reproduction

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives Describe hormonal changes that occur during puberty, the mechanisms that may control the onset of puberty, and the secondary sex characteristics that develop during puberty. Explain how the secretions of FSH and LH are regulated in the male and describe the actions of these hormones on the testes. Describe the stages of spermatogenesis and describe the effects of androgens on the male accessory sex organs. Describe oogenesis and the stages of follicle development through ovulation and formation of the corpus luteum.

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives (continued) Explain the hormonal interactions involved in the control of ovulation. Describe the changes in the secretion of ovarian sex steriods during a nonfertile cycle and explain the functions and fate of the corpus luteum. Explain how the secretion of FSH and LH is controlled through negative and positive feedback mechanisms during a menstrual cycle.

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Objectives (continued) Describe the cyclic changes that occur in the endometrium and the hormonal mechanisms that cause these changes. Describe the acrosomal reaction and the events that occur at fertilization, blastocyst formation and implantation. List the hormones secreted by the placenta and describe their actions. Discuss factors that stimulate uterine contractions during labor and parturition, and explain now the onset of labor may be regulated.

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sexual Determination Each zygote inherits 23 chromosomes from the mother and 23 chromosomes from the father. Produce 23 pairs of homologous chromosomes. First 22 pairs of chromosomes are autosomal chromosomes. 23 rd pair are sex chromosomes. Diploid cell undergoes meiotic division, its daughter cells receive only 1 chromosome from each homologous pair. The gametes are haploid. Chromosomal gender of zygote determined by fertilizing sperm.

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Formation of Testes First 40 days after conception the gonads of males and females are similar in appearance. Cells that will give rise to spermatogonia and oogonia migrate from yolk sac to developing embryonic gonads. Testis-determining factor (TDF) promotes the conversion to testes: Seminiferous tubules appear within 43-50 days following conception. Produce: Germinal cells: sperm. Nongerminal cells: Sertoli cells. Leydig cells: Appear about day 65.

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Formation of Testes (continued) Leydig cells secrete testosterone. Begins at the 8 th week and peaks at 12- 14 th week. Masculinizes embryonic structures. [Testosterone] then declines to very low levels until puberty. Testes descend into scrotum shortly before birth.

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Formation of Ovaries Absence of Y chromosome and TDF, female develop ovaries. Ovarian follicles do not appear until 2 nd trimester, about day 105.

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosomal Sex and Development of Embryonic Gonads Insert fig. 20.4

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Development of Accessory Sex Organs and Genitalia Presence or absence of testes determines the accessory sex organs and external genitalia. Male accessory organs derived from wolffian ducts. Sertoli cells secrete MIF (müllerian inhibition factor). Female accessory organs derived from mullerian ducts. Insert fig. 20.5

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Disorders of Embryonic Sexual Development Hermaphroditism: Both ovarian and testicular tissue is present in the body. Pseudohermaphrodite: Individual with either testes or ovaries but not both. Have accessory sex organs and external genitalia that are incompletely developed or inappropriate. Most common cause of female pseudohemaphroditism is congenital adrenal hyperplasia. In the male, one cause is testicular feminizing syndrome: Normal functioning testes, but lack receptors for testosterone.

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Regulation of Reproduction Hypothalamus releases LHRH (GnRH) into hypothalamo-hypophyseal portal vessels. Anterior pituitary secretes: LH (luteinizing hormone). FSH (follicle-stimulating hormone). Secreted in pulsatile fashion to prevent desensitization and down regulation of receptors.

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Interactions Anterior pituitary secretes LH and FSH. Secretion of LH and FSH stimulated by LHRH (GNRH). Primary effects of LH and FSH on gonads: Stimulation of spermatogenesis and oogenesis. Stimulation of gonadal hormone secretion. Maintenance of gonadal structure.

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Regulation Negative feedback: Inhibits GnRH from hypothalamus. Inhibits anterior pituitary response to GnRH. Inhibin secretion inhibits anterior pituitary release of FSH. Female: Estrogen and progesterone. Male: Testosterone. Insert fig. 20.9

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Onset of Puberty FSH and LH secretion is high in newborn, but falls to low levels in few weeks. At puberty: Brain maturation increases GnRH secretion. Decreased sensitivity of gonadotropin to negative feedback. During late puberty, pulsatile secretion of LH and FSH increase during sleep. Stimulate a rise in sex steroid secretion.

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Onset of Puberty (continued) Stimulates rise in testosterone and estradiol-17 . Produce secondary sexual characteristics. Age of onset related to the % of body fat and physical activity in the female Leptin secretion from adipocytes may be required for puberty. Insert fig. 20.10

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pineal Gland Secretes melatonin. Stimulated by postganglionic sympathetic neurons. Activity of these neurons is inhibited by nerve tracts that are activated by light. Secretion influenced by light-dark cycles. Inhibits gonadotropin secretion. Role in humans not established.

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 4 Phases of Human Sexual Response Excitation phase: Myotonia and vasocongestion. Engorgement of a sexual organ with blood. Erection of the nipples in both genders. Plateau phase: Clitoris becomes partially hidden. Erected nipples become partially hidden by swelling of areolae. Orgasm: Uterus and orgasmic platform of vagina contract. Contractions accompanying ejaculation. Resolution phase: Body returns to preexcitation conditions. Men enter refractory period.

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Male Reproductive System Testes: Seminiferous tubules: Contain receptor proteins for FSH in Sertoli cells. FSH stimulates spermatogenesis to occur. Leydig cells: LH stimulates secretion of testosterone. Contain receptor proteins for LH. Insert fig. 20.12

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Control of LH and FSH Secretion Negative feedback: Testosterone inhibits LH and GnRH production. Maintain relatively constant secretion of LH and FSH. Declines gradually in men over 50 years of age. Testosterone converted to DHT, which inhibits LH. Inhibin inhibits FSH secretion. Aromatization reaction producing estradiol in the brain, is required for the negative feedback effects. Insert fig. 20.13

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Derivatives of Testosterone Insert fig. 20.14

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Function of the Testes Testosterone and its derivatives are responsible for initiation and maintenance of body changes in puberty. Stimulate growth of muscles, larynx, and bone growth until sealing of the epiphyseal discs. Promote hemoglobin synthesis. Act in paracrine fashion, responsible for spermatogenesis. Insert fig. 20.15

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Estrogen Secretion Sertoli and Leydig cells secrete small amounts of estradiol. Receptors found in Sertoli and Leydig cells and accessory organs. May be responsible for: Negative feedback in brain. Sealing of epiphyseal plates. Regulatory function in fertility.

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Spermatogenesis Spermatogonia: Replicate initially by mitosis. One of the 2 primary spermatocytes undergoes meiosis: 2 nuclear divisions: 1 st meiotic division produces 2 secondary spermatocytes. 2 nd meiotic division produces 4 spermatids. Insert 20.16

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Spermiogenesis Maturation of spermatozoa. Phagocytosis of cytoplasm by the Sertoli cells. Cytoplasm is eliminated. Insert fig. 20.18

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sertoli Cells Form blood-testes barrier: Prevents autoimmune destruction of sperm. Produce FAS ligand which binds to the FAS receptor on surface to T lymphocytes, triggering apoptosis of T lymphocytes. Prevents immune attack. Secrete inhibin. Phagocytize residual bodies: May transmit information molecules from germ cells to Sertoli cells. Secrete androgen-binding protein (ABP): Binds to testosterone and concentrates testosterone in the tubules.

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormonal Control of Spermatogenesis Formation of primary spermatocytes and entry into early prophase I, begin during embryonic development. Spermatogenesis arrested until puberty. Testosterone required for completion of meiosis and spermatid maturation. Secrete paracrine regulators: IGF-1. Inhibin. Transforming growth factor. FSH necessary in the later stages of spermatid maturation.

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Male Accessory Organs Epididymis responsible for: Maturational changes. Resistance to pH changes and temperature. Storage of sperm between ejaculations. Ductus (vas) deferens: Carries sperm from epididymis into pelvic cavity. Seminal vesicles secrete: Fructose. Prostate secretes: Alkaline fluid. Citric acid. Ca 2+. Coagulation proteins.

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Erection, Emission, and Ejaculation Erection: Controlled by hypothalamus and spinal cord. Increased vasodilation of arterioles. Parasympathetic nervous system. NO is the NT. Blood flow into the erectile tissues of the penis. Emission: Movement of semen into the urethra. Stimulated by sympathetic nervous system. Ejaculation: Forcible expulsion of semen from the urethra out of the penis. Stimulated by sympathetic nervous system.

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Male Fertility 60-150 million sperm/ml ejaculate. Oligospermia: Sperm count of < 20 million/ml ejaculate. Decreased fertility caused by heat, pharmaceuticals, and illicit drugs. Male contraception: Compounds that suppress gonadotropin secretion. Testosterone. Progesterone and GnRH antagonist. Vasectomy: Each ductus deferens is cut and tied. Interferes with sperm transport. May develop anti-sperm antibodies.

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Female Reproductive System Ovaries: Contain a large number of follicles which enclose ova. Extensions called fimbriae partially cover each ovary. At ovulation, secondary oocyte is extruded. Fallopian (uterine) tubes: Ova drawn into the tubes by cilia.

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Female Reproductive System (continued) Uterus: Has 3 layers: Perimetrium: Outer layer of connective tissue. Myometrium: Smooth muscle layer. Endometrium: Inner layer of stratified, squamous, nonkeratinized epithelium. Shed during menstruation. Vagina: Cervical mucus plug.

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovarian Cycle 5 mo. gestation, ovaries contain 6-7 million oogonia. Oogenesis arrested in prophase of 1 st meiotic division (primary oocyte). Apoptosis occurs: 2 million primary oocytes at birth. 400,000 primary oocytes at puberty. 400 oocytes ovulated during the reproductive years. Insert fig. 20.30

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovarian Cycle (continued) Primary oocytes are contained in primary follicles. FSH stimulates granulosa cell growth. Develop into secondary follicles. Fusion of its vesicles to form the antrum. Mature graafian follicle. 1 st meiotic division completed (secondary oocyte). Polar body fragments. Insert fig. 20.32

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovarian Cycle (continued) Secondary oocyte confined to graafian follicle. Arrested at metaphase II. Under FSH stimulation: Theca cells secrete testosterone. Granulosa cells contain the enzyme aromatase to convert testosterone into estrogen. Granulosa cells form a ring (corona radiata) around oocyte and form mound (cumullus oophorus). Between oocyte and corona radiata is zona pellucida. Provides barrier to the sperm to fertilize the egg.

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovulation One graafian follicle forms bulge on surface of ovary. Extrudes secondary oocyte into the uterine tube. LH causes the empty follicle to become corpus luteum which secretes: Progesterone and estrogen. If not fertilized, becomes corpus albicans. Insert fig. 20.33

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pituitary-Ovarian Axis Hormonal interactions between the anterior pituitary and the ovaries. Anterior pituitary secretes FSH and LH. Controlled by GnRH. FSH secretion is slightly greater than LH during early phase of menstrual cycle. LH secretion greatly exceeds FSH secretion just prior to ovulation. - feedback.

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Menstrual Cycle Menstruation: Day 1-4/5. Day 1 is the first day of menstruation. Duration approximately 28 days. Secretions of estrogen and progesterone are at their lowest. Ovaries contain only primary follicles.

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Follicular Phase Lasts from day 1 to about 13. FSH: Follicles become increasingly sensitive to FSH. FSH stimulates the production of FSH receptors on the granulosa cells. Toward the end of the phase, sensitivity of FSH receptors increases. FSH and estradiol stimulate production of LH receptors in graafian follicle. Rapid rise in estradiol from granulosa cells. Negative feedback on LH and FSH.

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Follicular Phase (continued) Hypothalamus increases frequency of GnRH pulses. Augments the ability of anterior pituitary to respond to GnRH, to increase LH secretion. Positive feedback: LH surge begins 24 hours before ovulation. Triggers ovulation. FSH increase stimulates development of new follicles.

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Control of the Ovarian Cycle

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ovulation Wall of graafian follicle ruptures. Day 14. 1 st meiotic division is completed.

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Luteal Phase LH stimulates formation of the empty follicle into corpus luteum. Corpus luteum secretes: Progesterone: Plasma concentration rapidly rises. Exerts negative feedback on LH and FSH. Inhibin: Suppresses FSH secretion. Inhibin production decreases towards end of luteal phase.

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Luteal Phase (continued) Corpus luteum regresses unless fertilization occurs: Estradiol decreases. Progesterone decreases. Withdrawal of estradiol and progesterone cause menstruation to occur.

45. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cycle of Ovulation and Menstruation Insert fig. 20.35

46. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cyclic Changes in the Endometrium Proliferative Phase: Ovary is in follicular phase. Estradiol stimulates growth of endometrium of stratum functionale. Spiral arteries develop. Estradiol: Stimulate production of receptor proteins for progesterone.

47. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cyclic Changes in the Endometrium (continued) Secretory phase: Ovary is in luteal phase. Progesterone stimulates development of uterine glands, which become engorged with glycogen. Endometrium becomes thick, vascular, and spongy. Cervical mucus thickens and becomes sticky.

48. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cyclic Changes in the Endometrium (continued) Menstrual phase: Progesterone withdrawl causes constriction of spiral arteries. Necrosis and sloughing of endometrium occurs. Lasts 1-5 days.

49. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Contraceptive Methods Contraceptive pill: Synthetic estrogen combined with synthetic progesterone pills are taken once each day for 3 weeks after the last day of menstruation. Negative feedback inhibits ovulation. Placebo pill taken the 4 th week permits menstruation. Rhythm method: Women measure oral basal body temperature upon awakening daily. On day of LH surge, there is a slight drop in basal body temperature.

50. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Menopause Cessation of ovarian activity and menstruation. Age ~ 50 years. Ovaries are depleted of follicles. Estradiol and inhibin withdrawl causes hot flashes, and atrophy of the vaginal wall. LH and FSH increase.

51. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fertilization Ejaculation 300 million sperm, 100 reach (uterine) fallopian tube. Capacitation occurs. Fertilization occurs in the uterine tubes. Acrosome of sperm contains hyaluronidase, an enzyme that digests a channel through zona pellucida. Sperm fuses with ovum cell membrane. Insert 20.39

52. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fertilization (continued) As fertilization occurs, secondary oocyte completes 2 nd meiotic division. Sperm enters ovum cytoplasm. Ovum nuclear membrane disappears, zygote formed. Centrosome of zygote is derived from sperm cell. Insert fig. 20.41

53. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cleavage and Blastocyst Formation Cleavage: 30-36 hrs. after fertilization, the zygote divides by mitosis. About 50-60 hours after fertilization, the early embryo develops into morula. Blastocyst develops: Inner cell mass Fetus. Surrounding chorion: Trophoblasts form placenta. Insert fig. 20.43

54. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Implantation 6 th day after fertilization, blastocyst attaches to uterine wall. Trophoblast cells produce enzymes that allow blastocyst to burrow into endometrium. Insert fig. 20.45

55. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Embryonic Stem Cells and Cloning Only fertilized egg cells and early cleavage cells are totipotent: Ability to create the entire organism. Reproductive cloning: Adult stem cells can become totipotent if transplanted into egg cell cytoplasm. Therapeutic cloning: Nucleus transplantation to produce stem cells for purpose of growing specific tissue for the treatment of disease. Pluripotent: Cells obtained from inner cell mass of blastocyst (embryonic stem cells) can give rise to all tissues except the placenta. Multipotent: Can give rise to a number of differentiated cells.

56. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. hCG (Human Chorionic Gonadotropin) Trophoblast cells secrete hCG: Signals corpus luteum not to degenerate until placenta secretes adequate [hormones]. Prevents immunological rejection of implanting embryo. Has thyroid-stimulating ability. Produces effects similar to LH. Basis of pregnancy test. Insert fig. 20.46

57. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Placenta Syncytiotrophoblast secretes enzymes that create blood filled cavities in the maternal tissue. Cytotrophoblast then forms villi that grow into the pools of venous blood. Produces chorion frondosum on the side that faces the uterine wall. Other side of chorion bulges into the uterine cavity.

58. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Formation of the Placenta and Amniotic Sac Decidual reaction: Endometrial growth. Accumulation of glycogen. Decidua basalis: Maternal tissue in contact with the chorion frondosum. Decidua basalis and chorion fondosum together become placenta. Maternal and fetal blood do not mix. Insert fig. 20.50

59. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Amnion Envelop the embryo and umbilical cord. Amniotic fluid initially is isotonic, but as fetus develops; concentration changes by urine and sloughed cells of the fetus, placenta, and amniotic sac. Insert fig. 20.48

60. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Placenta Function Site for exchange of gases and other molecules between maternal and fetal blood. Gas exchange: 0 2 and C0 2. Nutrient exchange. Waste exchange. Synthesis of proteins and enzymes.

61. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Placental Hormones hCS (chorionic somatomammotropin): Actions similar to GH. Actions similar to prolactin. hCS and GH cause diabetic-like effect: Glucose sparing effects by maternal tissues. Ensure sufficient supply of glucose for placenta and fetus. Polyuria. Lipolysis.

62. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Placental Hormones (continued) Fetal-placental unit: Placenta must cooperate with the adrenal cortex in the fetus to produce estrogen. Estrogen/estriol stimulates: Endometrial growth. Inhibition of prolactin secretion. Growth of mammary ducts. Enlargement of mother’s uterus.

63. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Placental Hormones (continued) Progesterone: Suppresses uterine contractions. Stimulates uterine growth. Suppresses LH and FSH. Stimulates development of alveolar tissue of the mammary gland.

64. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parturition Estrogen in late pregnancy: Stimulates production of oxytocin receptors in myometrium. Produces receptors for prostaglandins. Produces gap junctions between myometrium cells in uterus. Factors responsible for initiation of labor are incompletely understood.

65. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parturition (continued) Insert fig. 20.52

66. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parturition (continued) Fetal adrenal cortex: Chain of events may be set in motion through CRH production. Fetal adrenal zone secretes DHEAS, which travel from fetus and placenta. Uterine contractions: Oxytocin. Prostaglandins.

67. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lactation Hypothalamus releases PRH. Anterior pituitary releases prolactin: Stimulates milk production. Prolactin secretion primarily controlled by PIH. Oxytocin needed for “milk letdown.”

68. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lactation (continued) Mammary gland: Lobules contain glandular alveoli that secrete milk of the lactating female. Alveoli secrete milk into secondary tubule that converge to form mammary duct. Ampulla: Where milk accumulates during nursing. Neuroendocrine reflex: Act of nursing maintains high levels of prolactin. Sucking may cause release of PRH.

69. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Insert fig. 20.55 Milk-Ejection Reflex